Ultrafast Hydrogen-Bonding Dynamics in Amyloid Fibrils.
Ultrafast Hydrogen-Bonding Dynamics in Amyloid Fibrils.
复制标题
淀粉样原纤维中的超快氢键动力学。
DOI：
10.1021/acs.jpcb.8b04642
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发表时间：
2018-12-13
期刊：
影响因子：
--
通讯作者：
Gai F
中科院分区：
文献类型：
--
作者：
Pazos IM;Ma J;Mukherjee D;Gai F
虽然有许多研究在生物系统中的氢键动力学的主题，很少，如果有的话，已经调查了淀粉样蛋白纤维的这一基本过程。在此，我们试图通过评估淀粉样蛋白纤维干界面中氢键的动态变化来深入了解这一主题。为了制备用于此目的的合适的模型肽系统，我们在形成淀粉样蛋白的Aβ16-22肽中引入两个突变。第一个是在19位的赖氨酸类似物，其用于帮助形成结构均匀的原纤维，第二个是在17位的天冬氨酸衍生物（DM），其旨在（1）用作位点特异性红外探针和（2）用作赖氨酸的氢键受体，使得可以在原纤维中形成β-折叠间氢键。使用红外光谱和原子力显微镜，我们表明（1）该突变肽确实形成了明确的原纤维，（2）当去除本体溶剂时，原纤维中不存在可检测的水，（3）用DM探针获得的红外结果与由以平行方式堆叠的两个反平行β-折叠组成的原纤维结构一致，导致形成预期的氢键。利用二维红外光谱，我们进一步表明，这种氢键的动力学发生在~2.3 ps的时间尺度上，这归因于赖氨酸的-NH 3+基团围绕其Cε-N π键的快速旋转。综上所述，这些结果表明：（1）DM是一种有用的红外标记物，有助于淀粉样蛋白原纤维的结构测定;（2）即使在淀粉样蛋白原纤维的紧密堆积的核心中，某些氨基酸侧链也可以进行超快运动，因此有助于系统的热力学稳定性。
While there are many studies on the subject of hydrogen bonding dynamics in biological systems, few, if any, have investigated this fundamental process in amyloid fibrils. Herein, we seek to add insight into this topic by assessing the dynamics of a hydrogen bond buried in the dry interface of amyloid fibrils. To prepare a suitable model peptide system for this purpose, we introduce two mutations into the amyloid-forming Aβ16-22 peptide. The first one is a lysine analog at position 19, which is used to help form structurally homogeneous fibrils, and the second one is an aspartic acid derivative (DM) at position 17, which is intended (1) to be used as a site-specific infrared probe and (2) to serve as a hydrogen-bond acceptor to lysine so that an inter-β-sheet hydrogen bond can be formed in the fibrils. Using both infrared spectroscopy and atomic force microscopy, we show that (1) this mutant peptide indeed forms well defined fibrils, (2) when bulk solvent is removed, there is no detectable water present in the fibrils, (3) infrared results obtained with the DM probe are consistent with a protofibril structure that is composed of two antiparallel β-sheets stacked in a parallel fashion, leading to formation of the expected hydrogen bond. Using two-dimensional infrared spectroscopy, we further show that the dynamics of this hydrogen bond occur on a timescale of ~2.3 ps, which is attributed to the rapid rotation of the –NH3+ group of lysine around its Cε-Nζ bond. Taken together, these results suggest that (1) DM is a useful infrared marker in facilitating structure determination of amyloid fibrils and (2) even in the tightly packed core of amyloid fibrils certain amino acid sidechains can undergo ultrafast motions, hence contributing to the thermodynamic stability of the system.
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DOI：
10.1016/j.bbapap.2005.10.021
发表时间：
2006-03-01
影响因子：
3.2
作者：
Meersman, F;Dobson, CM
通讯作者：
Dobson, CM
DOI：
10.1021/la302626d
发表时间：
2012-08-28
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
--
作者：
Measey TJ;Gai F
通讯作者：
Gai F
影响因子：
15
作者：
Esadze, Alexandre;Li, Da-Wei;Iwahara, Junji
通讯作者：
Iwahara, Junji
影响因子：
64.8
作者：
Lee, AL;Wand, AJ
通讯作者：
Wand, AJ
影响因子：
2.7
作者：
Linser, Rasmus;Sarkar, Riddhiman;Reif, Bernd
通讯作者：
Reif, Bernd